Long-Term Remission and Bone Marrow Findings in Children with Severe Aplastic Anemia Immunosuppressed with High Doses of Cyclophosphamide

Abstract

Background: Most cases of aplastic anemia are acquired and of autoimmune etiology. Treatment of patients lacking a stem cell donor habitually consists of two curses of immunosuppression with anti-thymocyte globuline plus cyclosporine (ATG/CSA), whereas intensive immunosuppression consisting exclusively of high doses of cyclophosphamide (HDCY) has been successfully employed mostly in adults, detailed long-term information on children receiving HDCY is lacking. Patients and methods: Five children suffering from severe acquired aplastic anemia and without an HLAcompatible stem cell donor were immunosuppressed with high-dose cyclophosphamide (HDCY) at a total dose of 200 mg/kg over four days. Granulocyte colony-stimulating factor (G-CSF) was administered at 5 μg/kg/day until sustained neutrophil and platelet count recovery. The surviving patients were followed-up for twelve years and their bone marrows examined at this time. Results:Three of the five children obtained a complete sustained hematological remission. Current ages are 17, 19 and 27. After twelve years of follow-up two patients have normal hematological values, with no relapse nor clonal or displasic hematological disorders, their bone marrow aspirate was morphologically normal, whereas bone marrow trephine biopsy histopathology demonstrated a reduced cell content to about 60% of normal. One patient developed myelodisplasia 12 years after HDCY and currently he is being considered for a bone marrow transplant. Conclusions: Sustained long-term trilineage hematopoiesis can be rescued in children suffering from SAA employing HDCY as the only immunosuppressor; the bone marrow did not fully recuperate its normal cellularity after twelve years post-treatment, mielodysplasia can develop more than ten years after HDCY.